Management of type 2 diabetes in patients with compensated liver cirrhosis: Short of evidence, plenty of potential

Background and aims: Treatment of type 2 diabetes (T2D) in patients with compensated cirrhosis is challenging due to hypoglycemic risk, altered pharmacokinetics, and the lack of robust evidence on the risk/benefit ratio of various drugs. Suboptimal glycemic control accelerates the progression of cirrhosis, while the frequent coexistence of nonalcoholic fatty liver disease (NAFLD) with T2D highlights the need for a multifactorial therapeutic approach. Methods: A literature search was performed in Medline, Google Scholar and Scopus databases till July 2023, using relevant keywords to extract studies regarding the management of T2D in patients with compensated cirrhosis. Results: Metformin, sodium-glucose co-transporter-2 inhibitors (SGLT2i), and glucagon-like peptide-1 receptor agonists (GLP-1 RA) are promising treatment options for patients with T2D and compensated liver cirrhosis, offering good glycemic control with minimal risk of hypoglycemia, while their pleiotropic actions confer benefits on NAFLD and body weight, and decrease cardiorenal risk. Sulfonylureas cause hypoglycemia, thus should be avoided, while in specific studies, dipeptidyl peptidase-4 inhibitors have been correlated with increased risk of decompensation and variceal bleeding. Despite the benefits of thiazolidinediones in nonalcoholic steatohepatitis, concerns about edema and weight gain limit their use in compensated cirrhosis. Insulin does not exert hepatotoxic effects and can be administered safely in combination with other drugs; however, the risk of hypoglycemia should be considered. Conclusions: The introduction of new hepatoprotective diabetes drugs into clinical practice, including tirzepatide, SGLT2i, and GLP-1 RA, sets the stage for future trials to investigate the ideal therapeutic regimen for people with T2D and compensated cirrhosis.